Cancer cachexia is wasting syndrome characterized in its early stages by a loss of host fat and protein stores without a concurrent change in food intake followed in its later stages with metabolic abnormalities. The cachectic syndrome is imposed by the tumor since weight gain and reversal of the metabolic abnormalities occurs when the tumor is removed. Tumor cells, like other cells, can not survive without substrate (carbon sources) from the host, and the intracellular metabolism of the tumor should reflect the availability of host-derived carbon sources. Differences in tumor metabolism have been reported which include increased glycolysis, lactogenesis and cholesterolgenesis. Do the differences in cellular metabolism between non-neoplastic and neoplastic tissue give tumor cells an advantage over the host that leads to loss of host fat stores? The answer can only be determined from quantitating production and utilization of substrate by the tumor and host separately, which has not been done. This study will focus on host and tumor metabolism in vivo separately and simultaneously to determined if the competition for substrate by tumor tissue to support its rapid and unregulated growth leads o the increased catabolism of the host's fat stores. These investigations will use [U13C] glucose and mass isotopomer technology to measure tumor, liver, muscle and fat intracellular metabolism; the tumor tissue-isolate model to measure substrate utilization of the tumor; and isotope tracers to measure host production of substrate (glucose production/6-3H-glucose, and lipolysis/1-14C-palmitate and [2H5] glycerol). Intracellular metabolism will focus on two active metabolic pathways: 1) glucose carbon recycling including lactate production and Krebs cycle parameters, and 2) glucose carbon channeling to lipid metabolites (cholesterol synthesis). The relative enrichments between precursor and labeled product will be used to estimate lactate production from labeling in lactate, Krebs cycle parameters from labeling in glutamate, aspartate, alanine, cholesterol synthesis from labeling in cholesterol, and ribose synthesis from labeling in ribose. Loss of substrate from the host to the tumor will be determined from the difference n host production of substrate and tumor utilization of substrate. After the intterelationship between tumor and host metabolism is known, I will investigate the effect of dietary fatty acids on host and tumor metabolism to determine if a specific diet can slow down or prevent the cancer cachexia process. In summary, results from this research will determine f substrate needs of the tumor deplete the host's substrate pool and if manipulation of dietary fat can alter tumor metabolism to benefit the host.